Comparison of Intra-operative Radiotherapy With Post-operative Radiotherapy for Women With Early Breast Cancer

NCT00983684 | Completed Phase 3 DMC

• 3 other identifiers: ISRCTN 34086741MREC No. 99/0307UKCRN ID 7265
• Study Type: interventional
• Target: 3,451
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether a single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence is equivalent to standard post-operative external beam radiotherapy after breast conserving surgery in women with early stage breast cancer in terms of local relapse within the treated breast.

Conditions

Invasive Breast Cancer; Breast Cancer

Keywords

Neoplasms by Site; Breast Neoplasms; Breast Diseases; Breast Cancer; Cancer of Breast; Cancer of the Breast; Carcinoma

Outcome Measures

Primary Outcomes (1)

• Local relapse within the treated breast.

  3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months

Secondary Outcomes (3)

• Site of relapse within the breast

  3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months

• Relapse-free survival and overall survival

  3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months

• Local toxicity/morbidity

  3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108, 120 months

Study Arms (2)

Intra-operative radiotherapy

EXPERIMENTAL

A single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence.

Device: Intrabeam

Post-operative radiotherapy

ACTIVE COMPARATOR

Standard post-operative radiotherapy.

Radiation: Post-operative radiotherapy

Interventions

Intrabeam DEVICE

A dose of 20 Gy at the surface of the applicator or 6 Gy at 1cm (in water) is prescribed by the radiation oncologist and delivered to the breast tissue. This takes approximately 30 minutes, depending on the size of the applicator.

Also known as: IORT, targeted intra-operative radiotherapy, TARGIT

Intra-operative radiotherapy

Post-operative radiotherapy RADIATION

All patients randomised to receive conventional radiotherapy within this trial should be treated in accordance with a pre-specified policy. Dosage should only be applied to the breast; axillary, supra-clavicular and internal mammary nodes should not generally be irradiated by discrete fields.

Also known as: EBRT

Post-operative radiotherapy

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 45 years or older
• Operable invasive breast cancer (T1 and small T2, N0-1, M0) confirmed by cytological or histological examination
• Suitable for breast conserving surgery
• Previously diagnosed and treated contralateral breast cancer may be entered but will be randomised to a separate stratum.
• Available for regular follow-up for at least ten years.
• Note: Individual centres may wish to restrict entry to a more exactly defined subset of patients, in which case, only patients with these characteristics may be entered by that particular centre. For example, centres may decide at outset to recruit only women over 50 or even over 65 years of age. Such policies must be pre-defined in writing and approved by the International Steering Committee.

You may not qualify if:

• More than one obvious cancer in the same breast as diagnosed by clinical examination, mammography or ultrasonography.
• Bilateral breast cancer at the time of diagnosis.
• Ipsilateral breast had a previous cancer and/or irradiation.
• Patients known to have BRCA2 gene mutations, but testing for gene mutations is not required
• Lobular cancer or Extensive intraductal Component (EIC =\>25% of the tumour is intraductal) on core biopsy or initial pathology (if performed)
• Patients undergoing primary medical treatment (hormones or chemotherapy) as initial treatment with neoadjuvant intent of reducing tumour size should be excluded; those given short duration (up to 4 weeks) systemic therapy can be included.
• Patients presenting with gross nodal disease, considered to be clinically malignant or proven cytologically or by scanning. In general, 4 or more positive nodes or extranodal spread are not suitable for Targit alone and should receive EBRT as well. However, individual centres may decide that anything more than micrometastasis should receive EBRT.
• Patients with any severe concomitant disease that may limit their life expectancy.
• Previous history of malignant disease does not preclude entry if the expectation of relapse-free survival at 10 years is 90% or greater.
• No more than 30 days can have elapsed between last breast cancer surgery (not axillary) and entry into the trial for patients in the post-pathology stratification.

Sponsors & Collaborators

• University College, London: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Clinical Trials Group

London, N19 5LW, United Kingdom

Location

Related Publications (6)

• Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sutterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet. 2010 Jul 10;376(9735):91-102. doi: 10.1016/S0140-6736(10)60837-9.

  PMID: 20570343 RESULT

• Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, Flyger HL, Massarut S, Alvarado M, Saunders C, Eiermann W, Metaxas M, Sperk E, Sutterlin M, Brown D, Esserman L, Roncadin M, Thompson A, Dewar JA, Holtveg HM, Pigorsch S, Falzon M, Harris E, Matthews A, Brew-Graves C, Potyka I, Corica T, Williams NR, Baum M; TARGIT trialists' group. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014 Feb 15;383(9917):603-13. doi: 10.1016/S0140-6736(13)61950-9. Epub 2013 Nov 11.

  PMID: 24224997 RESULT

• Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, Alvarado M, Douek M, Saunders C, Flyger H, Eiermann W, Brew-Graves C, Williams NR, Potyka I, Roberts N, Bernstein M, Brown D, Sperk E, Laws S, Sutterlin M, Corica T, Lundgren S, Holmes D, Vinante L, Bozza F, Pazos M, Blanc-Onfroy ML, Gruber G, Polkowski W, Dedes KJ, Niewald M, Blohmer J, McReady D, Hoefer R, Kelemen P, Petralia G, Falzon M, Joseph D, Tobias JS. New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer. Br J Cancer. 2021 Aug;125(3):380-389. doi: 10.1038/s41416-021-01440-8. Epub 2021 May 25.

  PMID: 34035435 DERIVED

• Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, Alvarado M, Douek M, Saunders C, Flyger HL, Eiermann W, Brew-Graves C, Williams NR, Potyka I, Roberts N, Bernstein M, Brown D, Sperk E, Laws S, Sutterlin M, Corica T, Lundgren S, Holmes D, Vinante L, Bozza F, Pazos M, Le Blanc-Onfroy M, Gruber G, Polkowski W, Dedes KJ, Niewald M, Blohmer J, McCready D, Hoefer R, Kelemen P, Petralia G, Falzon M, Joseph DJ, Tobias JS. Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial. BMJ. 2020 Aug 19;370:m2836. doi: 10.1136/bmj.m2836.

  PMID: 32816842 DERIVED

• Vaidya JS, Bulsara M, Saunders C, Flyger H, Tobias JS, Corica T, Massarut S, Wenz F, Pigorsch S, Alvarado M, Douek M, Eiermann W, Brew-Graves C, Williams N, Potyka I, Roberts N, Bernstein M, Brown D, Sperk E, Laws S, Sutterlin M, Lundgren S, Holmes D, Vinante L, Bozza F, Pazos M, Le Blanc-Onfroy M, Gruber G, Polkowski W, Dedes KJ, Niewald M, Blohmer J, McCready D, Hoefer R, Kelemen P, Petralia G, Falzon M, Baum M, Joseph D. Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer. JAMA Oncol. 2020 Jul 1;6(7):e200249. doi: 10.1001/jamaoncol.2020.0249. Epub 2020 Jul 9.

  PMID: 32239210 DERIVED

• Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Saunders C, Brew-Graves C, Potyka I, Morris S, Vaidya HJ, Williams NR, Baum M. An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial). Health Technol Assess. 2016 Sep;20(73):1-188. doi: 10.3310/hta20730.

  PMID: 27689969 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms by Site; Breast Diseases; Carcinoma

Condition Hierarchy (Ancestors)

Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Jeffrey S Tobias, MD FRCP FRCR

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2009
• First Posted: September 24, 2009
• Study Start: March 1, 2000
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: December 5, 2014

Record last verified: 2014-12

Locations

GB (1)